1. Cancer stem cells and their application into targeted therapy for cancer
Mol. Bio. Lab
Park Ji Won
Supervisor ; Dae Youn Hwang

2. Cancer
Multiple mutation
Uncontrolled growth
Cancers is an abnormal growth of cells caused by multiple changes in gene expression leading to dysregulated balance of cell proliferation and cell death.
Cancer can invade tissues and metastasize to distant sites, and it can cause death of the host.
Causes
Genetic factors : 5%
Environmental factors : 29%
Genetic mutation in stem cell : 66%
One in three people in the Western world develop cancer and one in five die of the disease.

3. Cancer therapy Surgery Radiation therapy Systematic therapy
Chemotherapy
Hormone therapy
Targeted drug therapy
In some cases, life prolonging effect is remarkable
In general, side effects are strong.
Not curative treatment
Lumpectomy
Lymph node dissection
Mastectomy
High curability
Loss of form of function
Unsuitable for elderly patient of patients with physical weakness
External beam
Brachytherapy
Intraoperative radiation
Non invasive treatment
High technology of RT can replace operation in some selected case
Limited side effects left

4. What is a Cancer stem cell (CSC)?
Normal Stem cells
Cancer stem cell
: Rare cells within organs with the ability to self-renew and give rise to all types of cells within the organ to drive organogenesis
: Rare cells within tumors with the ability to self-renew and give rise to the phenotypically diverse tumor cell population to drive tumorigenesis

5. The origin of Cancer stem cell (CSC)
Hierarchical Model
Clonal Evolution Model

6. Discovery of Cancer stem cell (CSC)
We fractionated AML cells on the basis of cell-surface-marker expression and found that the leukaemia-initiating cells that could engraft SCID mice to produce large numbers of colony-forming progenitors were CD34+CD38−
(A cell initiating human acute myeloid leukaemia after transplantation into SCID mice, Tsvee Lapldot et al., 1994)

7. Discovery of Cancer stem cell (CSC)
Breast cancer cells were heterogeneous with respect to expression of a variety of cell surface markers (including CD44, CD24, and B38.1). CD24 and CD44 are adhesion molecules whereas B38.1 has been described as a breast/ovarian cancer-specific marker. To determine whether these markers could distinguish tumorigenic from nontumorigenic cells.
(Prospective identification of tumorigenic breast cancer cells, Al-Haji et al., 2003)

8. Cancer stem cell (CSC) characteristics
Minor population in tumor : 0.1 – a few percent
Self-renewing : infinite proliferative potential.
Enhanced resistance to drugs, radiation, cell stress.
Tumorigenic : give rise to other cell types in tumor.
Associated with metastasis and relapse
Metastasis and relapse are involved in more than 90% of all cancer deaths
Strategies to eradicate CSCs are an urgent topic in cancer research

9. Hypoxia and metabolism
Cancer Stem cell niche and environment
Fibronectin/Collagen
Basal membrane
Cellular components
Extracellular matrix
Blood cells
Immune cells
Fibrolasts
Hormones
Cytokines
Exosomes
Secreted Factors
Hypoxia and metabolism
Calcium receptor
Lipids, Oxygen
Stem cell
Niche
Microenvironment around stem cells that provides support and signals regulating self-renewal and differentiation

10. Cancer stem cell (CSC) characteristics
CSC Resistance
DNA damage
Overexpression of Chk1/2 DNA damage repair protein
Downregulation of telomerase activity
Drug infiltration
Overexpression of efflux transporters from the ABC gene family
Apoptosis
Altered balance of signaling with FLT3 /Akt /Bcl /XIAP
Micro
-environment
Increased production of free-radical scavengers
Other
Slowed cell cycle kinetics
Increased molecular metabolism mediators

11. Cancer stem cell (CSC) Biomarker
Each type of cancer stem cell exhibits a unique set of molecular and biochemical markers.
Cancer cell biomarkers can be used to target residual cancer stem cells and used for targeted therapy.

12. The origin of Cancer stem cell (CSC)

13. Thank you 
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